Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells

  • Authors:
    • Ju Han Song
    • Seung Hyun Kim
    • Sin Ho Kweon
    • Tae Hyang Lee
    • Hee-Je Kim
    • Hyeoung-Joon Kim
    • Tae Sung Kim
  • View Affiliations

  • Published online on: April 1, 2009     https://doi.org/10.3892/ijo_00000245
  • Pages: 1165-1171
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Abstract

Resistance to cytarabine (Ara-C) incapacitates the therapeutic effort during the treatment of acute myeloid leukemia (AML). To elucidate mechanism responsible for the development of resistance to Ara-C, we established the Ara-C resistant AML-2/WT cell sublines, AML-2/IDAC and AML-2/ARC. We then conducted DNA microarray analysis to compare the AML-2/IDAC cells with parental AML-2/WT cells. The results of the microarray analysis revealed a severe defect in the expression of deoxycytidine kinase (dCK), which plays a key role in the transformation of Ara-C to the active form in AML-2/IDAC cells. A similar event was observed in AML-2/ARC cells, but not in Ara-C sensitive AML-2/IDA cells that were resistant to idarubicin. The decreased expression of dCK also resulted in lower activity in both Ara-C resistant variants. However, no significant difference in the intracellular concentration of Ara-C was observed among the cells tested, which indicates that the Ara-C resistant phenotype in our models occurred due to the lower expression and activity of dCK rather than a change in the ability to take up Ara-C. Additionally, in vitro assays using BM cells from AML patients revealed that the expression of dCK and the sensitivity to Ara-C were correlated. Taken together, these findings demonstrate that dCK can regulate the in vitro cellular response to Ara-C in AML cells.

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April 2009
Volume 34 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Song, J.H., Kim, S.H., Kweon, S.H., Lee, T.H., Kim, H., Kim, H., & Kim, T.S. (2009). Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells. International Journal of Oncology, 34, 1165-1171. https://doi.org/10.3892/ijo_00000245
MLA
Song, J. H., Kim, S. H., Kweon, S. H., Lee, T. H., Kim, H., Kim, H., Kim, T. S."Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells". International Journal of Oncology 34.4 (2009): 1165-1171.
Chicago
Song, J. H., Kim, S. H., Kweon, S. H., Lee, T. H., Kim, H., Kim, H., Kim, T. S."Defective expression of deoxycytidine kinase in cytarabine-resistant acute myeloid leukemia cells". International Journal of Oncology 34, no. 4 (2009): 1165-1171. https://doi.org/10.3892/ijo_00000245